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van Nistelrooij AM, van der Korput HA, Broer L, et al. Single nucleotide polymorphisms in CRTC1 and BARX1 are associated with esophageal adenocarcinoma. J Carcinog. 2015;14:5doi: 10.4103/1477-3163.157441.
van Nistelrooij, A. M., van der Korput, H. A., Broer, L., van Marion, R., van Berge Henegouwen, M. I., van Noesel, C. J., Biermann, K., Spaander, M. C., Tilanus, H. W., van Lanschot, J. J., Hofman, A., Uitterlinden, A. G., Wijnhoven, B. P., & Dinjens, W. N. (2015). Single nucleotide polymorphisms in CRTC1 and BARX1 are associated with esophageal adenocarcinoma. Journal of carcinogenesis, 145. https://doi.org/10.4103/1477-3163.157441
van Nistelrooij, Anna M J, et al. "Single nucleotide polymorphisms in CRTC1 and BARX1 are associated with esophageal adenocarcinoma." Journal of carcinogenesis vol. 14 (2015): 5. doi: https://doi.org/10.4103/1477-3163.157441
van Nistelrooij AM, van der Korput HA, Broer L, van Marion R, van Berge Henegouwen MI, van Noesel CJ, Biermann K, Spaander MC, Tilanus HW, van Lanschot JJ, Hofman A, Uitterlinden AG, Wijnhoven BP, Dinjens WN. Single nucleotide polymorphisms in CRTC1 and BARX1 are associated with esophageal adenocarcinoma. J Carcinog. 2015 May 21;14:5. doi: 10.4103/1477-3163.157441. eCollection 2015. PMID: 26085818; PMCID: PMC4453126.
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J Carcinog. 2015 May 21;14:5. doi: 10.4103/1477-3163.157441. eCollection 2015.

Single nucleotide polymorphisms in CRTC1 and BARX1 are associated with esophageal adenocarcinoma.

Journal of carcinogenesis

Anna M J van Nistelrooij, Hetty A G M van der Korput, Linda Broer, Ronald van Marion, Mark I van Berge Henegouwen, Carel J van Noesel, Katharina Biermann, Manon C W Spaander, Hugo W Tilanus, J Jan B van Lanschot, Albert Hofman, André G Uitterlinden, Bas P L Wijnhoven, Winand N M Dinjens

Affiliations

  1. Department of Pathology, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, The Netherlands ; Department of Surgery, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, The Netherlands.
  2. Department of Pathology, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, The Netherlands.
  3. Department of Internal Medicine, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, The Netherlands.
  4. Department of Surgery, Academic Medical Centre, Amsterdam, The Netherlands.
  5. Department of Pathology, Academic Medical Centre, Amsterdam, The Netherlands.
  6. Department of Gastroenterology and Hepatology, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, The Netherlands.
  7. Department of Surgery, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, The Netherlands.
  8. Department of Epidemiology, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, The Netherlands.
  9. Department of Internal Medicine, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, The Netherlands ; Department of Epidemiology, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, The Netherlands.

PMID: 26085818 PMCID: PMC4453126 DOI: 10.4103/1477-3163.157441

Abstract

OBJECTIVE: Recently, single nucleotide polymorphisms (SNPs) associated with esophageal adenocarcinoma (EAC) and Barrett's esophagus (BE) were identified; rs10419226 (CRTC1), rs11789015 (BARX1), rs2687201 (FOXP1), rs2178146 (FOXF1), rs3111601 (FOXF1), and rs9936833 (FOXF1). These findings indicate that genetic susceptibility could play a role in the initiation of EAC in BE patients. The aim of this study was to validate the association between these previously identified SNPs and the risk of EAC in an independent and large case-control study.

DESIGN: Six SNPs found to be associated with EAC and BE were genotyped by a multiplex SNaPshot analysis in 1071 EAC patients diagnosed and treated in the Netherlands. Allele frequencies were compared to a control group derived from the Rotterdam Study, a population-based prospective cohort study (n = 6206). Logistic regression analysis and meta-analysis were performed to calculate odds ratios (OR).

RESULTS: Rs10419226 (CRTC1) showed a significantly increased EAC risk for the minor allele (OR = 1.17, P = 0.001), and rs11789015 (BARX1) showed a significantly decreased risk for the minor allele (OR = 0.85, P = 0.004) in the logistic regression analysis. The meta-analysis of the original GWAS and the current study revealed an improved level of significance for rs10419226 (CRTC1) (OR = 1.18, P = 6.66 × 10(-10)) and rs11789015 (BARX1) (OR = 0.83, P = 1.13 × 10(-8)).

CONCLUSIONS: This independent and large Dutch case-control study confirms the association of rs10419226 (CRTC1) and rs11789015 (BARX1) with the risk of EAC. These findings suggest a contribution of the patient genetic make-up to the development of EAC and might contribute to gain more insight in the etiology of this cancer.

Keywords: Barrett's esophagus; esophageal adenocarcinoma; single nucleotide polymorphisms

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